vaccine therapy in treating patients undergoing surgery for recurrent glioblastoma multiforme

Conditions: Recurrent Central Nervous System Neoplasm

Summary: rationale: vaccines made from a person's tumor cells and dendritic cells may help the body build an effective immune response to kill tumor cells. purpose: this phase i trial is studying the side effects of vaccine therapy in treating patients undergoing surgery for recurrent glioblastoma multiforme (gbm).

objectives: primary * to evaluate the feasibility and safety of an autologous brain tumor stem cell messenger ribonucleic acid (mrna)-loaded dendritic cell vaccine in adult patients with recurrent glioblastoma multiforme. secondary * to assess humoral and cellular immune responses to vaccination. * to compare the proportion of vaccinated patients alive at 6 months from the time of surgery for recurrent tumor with matched historical cohorts. outline: patients undergo surgical resection of tumor. tumor tissue samples are collected to isolate brain tumor stem cells (btscs) and for extraction and amplification of btsc-specific mrna. within 4 weeks after surgical resection, patients undergo leukapheresis over 4 hours to generate dendritic cells (dcs). patients also undergo leukapheresis at 1 week after the third vaccination and then at least every 3 months as needed for generation of additional dcs. patients receive autologous btsc mrna-loaded dc vaccine intradermally once weekly for 3 weeks and then once monthly in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed periodically.

Eligibility criteria:
inclusion criteria: * age \>18 years of age * first recurrence of gbm (who grade iv glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of gbm * no known contraindications to receiving avastin * karnofsky performance status (kps) of \> 70% * radiation therapy (rt) with ≥ 45 gy tumor dose, completed ≥ 8 weeks prior to study entry exclusion criteria: * contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal) * clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment * pregnant or need to breast feed during the study period (negative beta-human chorionic gonadotropin (hcg) test required), or unable to maintain use of contraception while on study * active infection requiring treatment or an unexplained febrile (\> 101.5 degrees f) illness * known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, hepatitis b or hepatitis c * unstable or severe intercurrent medical conditions such as severe heart (new york association class 3 or 4) or lung (fev1 \< 50%) disease, uncontrolled diabetes mellitus * prior brachytherapy, carmustine wafer therapy, radiolabeled monoclonal antibodies, or stereotactic radiosurgery * prior inguinal lymph node dissection avastin-specific exclusion criteria subjects meeting any of the following criteria are ineligible for study entry: * inadequately controlled hypertension (defined as systolic blood pressure \>150 mmhg and/or diastolic blood pressure \> 100 mmhg) * prior history of hypertensive crisis or hypertensive encephalopathy * new york heart association (nyha) grade ii or greater congestive heart failure * history of myocardial infarction or unstable angina within 6 months prior to enrollment * history of stroke or transient ischemic attack within 6 months prior to enrollment * significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to enrollment) * history of hemoptysis (\> or = 1/2 teaspoon of bright red blood per episode) within 28 days prior to enrollment * evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment * core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment * serious, non-healing wound, active ulcer or untreated bone fracture * proteinuria as defined by \> +1 on urinalysis dipstick * known hypersensitivity to any component of avastin * pregnant (positive pregnancy test) or lactation

Keywords: adult giant cell glioblastoma adult glioblastoma adult gliosarcoma adult astrocytoma recurrent adult brain tumor